The following discussion of the background of the invention is merely provided to aid the reader in understanding the invention and is not admitted to describe or constitute prior art to the present invention.
Asymmetric dimethylarginine (ADMA) is an arginine derivative formed by methylation of arginine residues in proteins, followed by protein hydrolysis. ADMA has been reported to regulate rates of nitric oxide (NO) formation, which can act as a signal molecule in the nervous system, an anti-infective, a regulator of blood pressure, and a regulator of blood flow. Elevated ADMA is reportedly a risk factor for hypertension, cardiovascular disease, renal failure, and erectile dysfunction. Factors contributing to elevated ADMA include increased oxidative challenge and folic acid insufficiency. See, e.g., WO04046314, which is hereby incorporated in its entirety.
In developing a binding assay for ADMA, the artisan must consider that samples may contain symmetrical dimethylarginine (SDMA) and/or arginine. Thus, immunogenic and label conjugates should be designed to present arginine or its N-methyl derivatives in a manner that permits specific recognition and discrimination of molecules which differ only in the methylation state of the two equivalent nitrogens on the guanidino group. Analogs for use in preparing such conjugates should also be designed to provide convenient attachment to various proteins, polypeptides, and labels under mild conditions.